Podocalyxin Is A Marker Of Poor Prognosis In Colorectal Cancer

Background: Over two decades ago, a proposal was that two different colorectal cancer (CRC) entities existed,
based on tumour location either proximal (right) or distal (left) of the splenic flexure. Proximal and distal tumours
exhibit different clinical, epidemiological, and biological characteristics. Improvement of the prognostic evaluation
of CRC requires new molecular markers. Podocalyxin-like 1 (PODXL), an anti-adhesive transmembrane sialomucin, is
associated with an aggressive tumour phenotype and poor prognosis. For colorectal cancer, it has been suggested
to be a marker of poor prognosis. The aim of this study was to investigate the role of PODXL in CRC by use of a
novel monoclonal antibody.Methods: In 1983–2001, 840 consecutive colorectal cancer patients were treated at Helsinki University Central
Hospital, of whom 767 were successfully scored for PODXL immunohistochemical expression from tumour tissue
microarrays by use of a novel monoclonal in-house antibody. Associations of PODXL expression and tumour
location with other clinicopathological variables were explored by Fisher’s exact-test, linear-by- linear association
test, and binary logistic regression. Survival analyses were done by the Kaplan-Meier method and Cox proportional
hazards model.Results: PODXL protein expression was high in 44 (5.7%) specimens. High expression associated strongly with poor
differentiation (p < 0.0001), advanced stage (p = 0.011), and location of the tumour in the right hemicolon (RHC)
(p < 0.001). Tumours of the RHC were more poorly differentiated (p < 0.0001) and showed higher PODXL expression
(p < 0.001). High PODXL expression associated significantly with higher risk for disease-specific death from CRC (hazard ratio
(HR) = 2.00; 95% confidence interval (CI) 1.31–3.06, p = 0.001) and also in the subgroups of left hemicolon (LHC)
cancers (HR = 2.60; 95% CI 1.45–4.66, p = 0.001) and rectal cancers (HR = 3.03; 95% CI 1.54–5.60, p = 0.001). Results
remained significant in multivariable analysis (respectively, HR = 1.82; 95% CI 1.15–2.86, p = 0.01; HR = 2.59; 95% CI
1.41–4.88, p = 0.002; and HR = 2.69; 95% CI 1.30–5.54, p = 0.007). Conclusion: Podocalyxin was an independent factor for poor prognosis in colorectal cancer and in the subgroups of left hemicolon and rectum. This is, to our knowledge, the first evidence of such difference in PODXL expression, its function possibly being dependent upon tumour location.